Document Detail


Inhibitory effects of osemozotan, a serotonin 1A-receptor agonist, on methamphetamine-induced c-Fos expression in prefrontal cortical neurons.
MedLine Citation:
PMID:  19336914     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Psychostimulants induce hyperlocomotion in normal subjects, although, they are effective in producing a calming effect in hyperactive subjects. This paradoxical effect has been related to changes in serotonin (5-HT) neurotransmission in hyperactive dopamine transporter-knockout mice. In addition, we observed that hyperlocomotion in mice lacking pituitary adenylate cyclase-activating polypeptide was attenuated by amphetamine dependent on 5-HT(1A) receptor signaling and that amphetamine, when co-administered with a 5-HT(1A) agonist, produced a calming effect in wild-type mice. Here, in an attempt to address how 5-HT(1A) receptor signaling exerts the calming action of psychostimulants, we examined c-Fos expression in several brain regions after administration of methamphetamine and osemozotan, a selective 5-HT(1A) receptor agonist. The number of c-Fos-positive cells was increased in the medial prefrontal cortex, striatum and nucleus accumbens in methamphetamine (3 mg/kg body weight)-injected mice. Osemozotan (1 mg/kg) significantly reduced the methamphetamine-induced c-Fos expression in the medial prefrontal cortex and striatum, but not in the nucleus accumbens. This osemozotan action was completely blocked by the 5-HT(1A) receptor antagonist WAY-100635 (1 mg/kg). As the prefrontal cortex is considered to be involved in the beneficial actions of psychostimulant medications for attention-deficit/hyperactivity disorder, the present result showing 5-HT(1A)-mediated inhibition of corticostriatal activity may partly be related to this psychostimulant action.
Authors:
Rie Tsuchida; Masahiro Kubo; Norihito Shintani; Michikazu Abe; Katalin Köves; Kazuki Uetsuki; Mariko Kuroda; Hitoshi Hashimoto; Akemichi Baba
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biological & pharmaceutical bulletin     Volume:  32     ISSN:  0918-6158     ISO Abbreviation:  Biol. Pharm. Bull.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-01     Completed Date:  2009-05-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9311984     Medline TA:  Biol Pharm Bull     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  728-31     Citation Subset:  IM    
Affiliation:
Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Central Nervous System Stimulants / pharmacology*
Dioxanes / antagonists & inhibitors,  pharmacology*
Dioxoles / antagonists & inhibitors,  pharmacology*
Gene Expression / drug effects
Genes, fos / drug effects*
Immunohistochemistry
Male
Methamphetamine / pharmacology*
Mice
Mice, Inbred ICR
Neostriatum / cytology,  drug effects,  metabolism
Neurons / drug effects*,  metabolism*
Piperazines / pharmacology
Prefrontal Cortex / cytology*,  drug effects,  metabolism*
Pyridines / pharmacology
Receptor, Serotonin, 5-HT1A / agonists*
Serotonin Agonists / pharmacology*
Serotonin Antagonists / pharmacology
Chemical
Reg. No./Substance:
0/Central Nervous System Stimulants; 0/Dioxanes; 0/Dioxoles; 0/MKC 242; 0/Piperazines; 0/Pyridines; 0/Serotonin Agonists; 0/Serotonin Antagonists; 112692-38-3/Receptor, Serotonin, 5-HT1A; 146714-97-8/WAY 100635; 537-46-2/Methamphetamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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